Role of Cystathionine β-Synthase and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics of Murine Breast Cancer Cells DOI Creative Commons
Sidnéia Sousa Santos, Larissa de Oliveira Cavalcanti Peres Rodrigues, Vanessa Martins

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 647 - 647

Published: March 5, 2023

Cystathionine β-synthase (CBS), CSE (cystathionine γ-lyase) and 3-mercaptopyruvate sulfurtransferase (3-MST) have emerged as three significant sources of hydrogen sulfide (H2S) in various forms mammalian cancer. Here, we investigated the functional role CBS’ 3-MST’s catalytic activity murine breast cancer cell line EO771. The CBS/CSE inhibitor aminooxyacetic acid (AOAA) 3-MST 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) were used to assess endogenous H2S modulation proliferation, migration, bioenergetics viability vitro. Methods included measurements (MTT LDH assays), proliferation vitro wound healing (IncuCyte) cellular (Seahorse extracellular flux analysis). CBS 3-MST, well expression detected by Western blotting; production was measured fluorescent dye AzMC. results show that EO771 cells express CBS, protein, several enzymes involved degradation (SQR, TST, ETHE1). Pharmacological inhibition or inhibited production, suppressed attenuated proliferation. Cell migration only inhibitor, but not inhibitor. Inhibition did significantly affect basal viability; (but CBS/CSE) slightly enhanced cytotoxic effects oxidative stress (hydrogen peroxide challenge). From these findings, conclude H2S, generated a lower degree CBS/CSE, contributes maintenance bioenergetics, may also exert minor cytoprotectant.

Language: Английский

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer DOI Creative Commons
Alyaa Dawoud, R.A. Youness,

Heba Nafea

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 16, 2024

Abstract Background Hydrogen sulfide (H 2 S) is a significant endogenous mediator that has been implicated in the progression of various forms cancer including breast (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are three principal mammalian enzymes responsible for H S production. Overexpression CBS, CSE 3MST was found to be associated with poor prognosis BC patients. Moreover, linked an immune-suppressive tumor microenvironment BC. Recently it observed cells, response single or dual inhibition synthesizing enzymes, develop escape mechanism by overexpressing alternative sources generation. Thus, aim this work compensatory pan repressing using microRNAs (miRNAs) investigate their impact on oncogenic immunogenic profile cells. Methods female patients ( n = 25) were recruited. In-silico analysis used identify miRNAs targeting CSE, 3MST. MDA-MB-231 cells cultured transfected oligonucleotides. Total RNA extracted Biazol, reverse transcribed quantified qRT-PCR. levels measured AzMc assay. hallmarks assessed trans-well migration, wound healing, MTT, colony forming assays. Results miR-193a miR-548c validated eight different bioinformatics software simultaneously target MiR-193a significantly downregulated tissues compared non-cancerous counterparts. Ectopic expression TNBC resulted marked repression transcript protein levels, decrease reduction cellular viability, migration ability, immune-suppressor proteins GAL3 GAL9, CD155 upregulation immunostimulatory MICA MICB proteins. Conclusion This study sheds light onto as potential pan-repressors enzymes. identifies them novel suppressor immunomodulatory TNBC.

Language: Английский

Citations

6
Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis DOI Creative Commons
Eugenia Piragine,

Marco Andrea Malanima,

Ersilia Lucenteforte

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1023 - 1023

Published: June 21, 2023

Hydrogen sulfide (H2S) is an endogenous gasotransmitter that promotes multiple biological effects in many organs and tissues. An imbalanced biosynthesis of H2S has been observed animal models age-related pathological conditions. However, the results from human studies are inconsistent. We performed a systematic review with meta-analysis searched Medline, Embase, Scopus, CENTRAL databases. included observational on patients diseases showing levels blood, plasma, or serum. All analyses were carried out R software. 31 21 meta-analysis. The circulating significantly reduced progressive, chronic, degenerative compared healthy people (standardized mean difference, SMD: −1.25; 95% confidence interval, CI: −1.98; −0.52). When we stratified by type disorder, significant reduction vascular disease (e.g., hypertension) (SMD: −1.32; −2.43; −0.22) kidney −2.24; −4.40; −0.08) control group. These could support potential use compounds targeting “H2S system” to slow down progression elderly.

Language: Английский

Citations

14
Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems DOI Open Access
Aisha Farhana, Abdullah Alsrhani, Yusuf S. Khan

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3836 - 3836

Published: July 28, 2023

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory conventional diagnostic chemotherapeutics due their limited targetability, specificity, solubility, side effects. The inherent ability of each cancer evolve through various genetic epigenetic transformations metabolic reprogramming underlies limitations. Though tumor microenvironments (TMEs) quite well understood some cancers, microenvironment differs from other internal perturbations skew thereby impeding development appropriate diagnostics, drugs, vaccines, therapies. associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation resistant niches progression, a thorough understanding crucial However, this remains missing element theranostics, necessitating modalities that can be adapted for diagnostics therapeutics. In challenging scenario, nanomaterials modular platforms TME achieving successful theranostics. Several nanoscale particles have been successfully researched animal models, few reached clinical trials, achieved Nanoparticles exhibit intrinsic capability interact with diverse biomolecules modulate functions. Furthermore, nanoparticles functionalized receptors, modulators, drugs facilitate specific targeting reduced toxicity. This review discusses current different theranostic nanosystems, synthesis, functionalization, targetability modulation bioenergetics, microenvironment. We highlight potential nanosystems enhanced chemotherapeutic success emphasizing questions remain unanswered.

Language: Английский

Citations

13
Dietary methionine restriction in cancer development and antitumor immunity DOI
Ming Ji, Qing Xu, Xiaoling Li

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(5), P. 400 - 412

Published: Feb. 20, 2024

Language: Английский

Citations

5
Bridging the Gap in Cancer Research: Sulfur Metabolism of Leukemic Cells with a Focus on L-Cysteine Metabolism and Hydrogen Sulfide-Producing Enzymes DOI Creative Commons
Konrad Kaleta, Klaudia Janik, Leszek Rydz

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 746 - 746

Published: June 24, 2024

Leukemias are cancers of the blood-forming system, representing a significant challenge in medical science. The development leukemia cells involves substantial disturbances within cellular machinery, offering hope search for effective selective treatments that could improve 5-year survival rate. Consequently, pathophysiological processes focus critical research. Enzymes such as cystathionine beta-synthase and sulfurtransferases like thiosulfate sulfurtransferase, 3-mercaptopyruvate gamma-lyase play vital role sulfur metabolism. These enzymes essential to maintaining homeostasis, providing robust antioxidant defenses, supporting cell division. Numerous studies have demonstrated cancerous can alter expression activity these enzymes, uncovering potential vulnerabilities or molecular targets cancer therapy. Recent laboratory research has indicated certain lines may exhibit changes patterns enzymes. Analysis scientific literature online datasets confirmed variations enzyme function specific leukemic compared normal leukocytes. This comprehensive review collects analyzes available information on lines, valuable insights identifying new pathways this field.

Language: Английский

Citations

5
Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression DOI Creative Commons
Constantin Munteanu, Anca‐Irina Galaction, Mădălina Poştaru

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1951 - 1951

Published: Aug. 26, 2024

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation potential cardiovascular events. Key players in ECM inflammation are metalloproteinases (MMPs) CD147/EMMPRIN, surface glycoprotein expressed on cells, vascular smooth muscle cells (VSMCs), immune that regulates MMP activity. Hydrogen sulfide (H₂S), gaseous signaling molecule, has emerged as significant modulator of these processes including oxidative stress mitigation, reduction, remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs CD147/EMMPRIN assesses its impact atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, Web Science databases, focusing studies examining modulation contexts. Findings indicate modulates expression activity transcriptional regulation post-translational modifications, S-sulfhydration. By mitigating stress, reduces activation, contributing stability also downregulates via pathways, diminishing responses cellular proliferation plaques. The dual regulatory role inhibiting downregulating CD147 suggests therapeutic agent stabilizing atherosclerotic plaques inflammation. Further research warranted elucidate precise molecular mechanisms explore H₂S-based therapies for clinical application atherosclerosis.

Language: Английский

Citations

5
Copper-Based Nanomedicines for Cuproptosis-Mediated Effective Cancer Treatment DOI Creative Commons

Dahye Noh,

Hokyung Lee,

Sangmin Lee

et al.

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

Language: Английский

Citations

5
Sequential Accumulation of ‘Driver’ Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids DOI Creative Commons
Kelly Ascenção, Nahzli Dilek, Karim Zuhra

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(9), P. 1823 - 1823

Published: Sept. 15, 2022

Recently, a CRISPR-Cas9 genome-editing system was developed with introduced sequential 'driver' mutations in the WNT, MAPK, TGF-β, TP53 and PI3K pathways into organoids derived from normal human intestinal epithelial cells. Prior studies have demonstrated that isogenic harboring tumor suppressor genes APC, SMAD4 TP53, as well oncogene KRAS, assumed more proliferative invasive properties vitro vivo. A separate body of implicates role various hydrogen sulfide (H2S)-producing enzymes pathogenesis colon cancer. The current study designed to determine if above pathway affect expression H2S producing enzymes. Western blotting used detect H2S-producing cystathionine β-synthase (CBS), γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST), several key involved degradation such thiosulfate sulfurtransferase/rhodanese (TST), ethylmalonic encephalopathy 1 protein/persulfide dioxygenase (ETHE1) sulfide-quinone oxidoreductase (SQR). levels were detected by live-cell imaging using fluorescent probe. Bioenergetic parameters assessed Extracellular Flux Analysis; markers epithelial-mesenchymal transition (EMT) blotting. results show consecutive produced gradual upregulations CBS expression-in particular its truncated (45 kDa) form-as CSE 3-MST expression. In advanced organoids, when upregulation coincided downregulation H2S-degrading enzyme SQR, increased generation also detected. This effect cellular bioenergetics (mitochondrial respiration and/or glycolysis) an Wnt/β-catenin pathway, effector EMT. Thus cells according Vogelstein sequence are associated multiple generating pathways, which, turn, translates functional changes dedifferentiation, aggressive cancer phenotypes.

Language: Английский

Citations

19
Versatile roles of cysteine persulfides in tumor biology DOI Creative Commons

Klaudia Borbényi-Galambos,

Ágnes Czikora,

Katalin Erdélyi

et al.

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 79, P. 102440 - 102440

Published: Feb. 28, 2024

Rewiring the transsulfuration pathway is recognized as a rapid adaptive metabolic response to environmental conditions in cancer cells support their increased cysteine demand and produce Reactive Sulfur Species (RSS) including hydrogen sulfide (H

Language: Английский

Citations

4
Cellular Signaling of Amino Acid Metabolism in Prostate Cancer DOI Open Access

Ping Yao,

Shiqi Cao, Zhiguang Zhu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 776 - 776

Published: Jan. 17, 2025

Prostate cancer is one of the most common malignancies affecting men worldwide and a leading cause cancer-related mortality, necessitating deeper understanding its underlying biochemical pathways. Similar to other types, prostate also characterised by aberrantly activated metabolic pathways that support tumour development, such as amino acid metabolism, which involved in modulating key physiological pathological cellular processes during progression this disease. The metabolism several acids, glutamine methionine, crucial for tumorigenesis, dysregulated commonly discussed cancer. And roles some less studied histidine glycine, have been covered studies. Aberrant regulation two major signalling pathways, mechanistic target rapamycin (mTOR) general control non-depressible 2 (GCN2), driver reshaping landscape By summarising our current how modulated cancer, here, we provide further insights into certain potential therapeutic targets managing through interventions.

Language: Английский

Citations

0